Safety of glyburide for gestational diabetes: a metaanalysis of pregnancy outcomes. Ann Pharmacother 2008;42:483–490

Gestational diabetes mellitus compli-cates an estimated 4 % of all preg-nancies and is associated with increased perinatal risks, including macrosomia, perinatal death, and hypoglycemia.1 Cur-rently, the mainstay of therapy is diet and insulin. Traditionally, oral hypoglycemic drugs have not been widely used be-cause of the potential risk of fetal and neonatal hypoglycemia associated with their placental transfer to the fetus.2 A breakthrough experimental study has shown minimal placental transfer of glyburide across the perfused placental lobule.3 Direct measurement of glyburide showed undetectable umbilical levels in the presence of therapeutic maternal con-centrations.4 Subsequent work has shown active transport of glyburide from the fe-tal to the maternal circulation carried out by adenosine binding cassette placental transporters, including multidrug resis-tant–associated protein mdr 1 and mdr 3 and breast cancer–resistant protein.5,6 Treatment of gestational diabetes with insulin has major challenges: women with this condition have been mostly healthy and the need to inject insulin dai-ly may be associated with impaired ad-herence and, subsequently, poorer preg-nancy outcomes.7 Another significant factor is that the cost of insulin and the associated devices required for its injection are financially prohibitive and are not affordable in many parts of the world.8 Hence, glyburide would present a number of ad-vantages. If, indeed, the placental transfer of glyburide is minimal and risks to the fetus are not greater than risks with insulin treatment, then the drug may be a safe alterna-tive for the treatment of gestational diabetes. The overall estimate of glyburide safety is not known. Although studies have supported its relative safety,4 their sample size was not sufficiently powered to document perinatal safety. For example, the double-blind, random